Food Regulates Genes: The Familial Dysautonomia Example

When we think of genetics, of DNA, we think of something fixed or hardwired. This has been the predominant dogma of the last century and still is to some extent. Contrary to our rather deterministic expectations, however, DNA is not the immutable blue print for health and disease that we once thought. It is quite malleable. In fact, it is malleable by design. That is, it is adaptive to the environment in ways that we are only yet beginning to understand. Environmental stressors of any color change the activity and conformation of genetic material, sometimes subtly flicking on or off a particular protein with slight chemical alterations at critical junctures, and sometimes quite radically changing the DNA itself by adducting molecules and/or rearranging the very language of the scripts. Those changes are then passed down from parent to offspring, only to be modified further by the environments of each subsequent generation. The result is a complex phenotype of health and disease that is at once foundational, inasmuch as it provides the backbone of existence, but also, surprisingly plastic or modifiable, perhaps more so than we can even imagine. Food, it turns out, is one of the key drivers in genetic malleability. Sit with that for a moment. Food alters genes.

Familial Dysautonomia: The Connection between Genes and Environment

Over the course of writing our book, Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition, I came across many examples of genetic malleability. A particularly striking example involves a devastating condition called Familial Dysautonomia. Familial dysautonomia, also known as “Riley-Day Syndrome” is a relatively rare condition affecting approximately 1 in 3700 individuals of Ashkenazic Jewish heritage. It presents in infancy and carries with it a high mortality rate. Infants carrying the underlying mutation have a increased susceptibility to infection and sudden death. Some of the symptoms associated with familial dysautonomia include:

A failure to grow despite normal growth hormone

Difficulty in feeding, choking, and defective swallowing coupled with a failure to thrive

Severe episodes of vomiting

Anorexia

The absence of fungiform papillae and taste buds on the tongue

Excessive sweating, especially on the head during sleep

A failure to produce tears

Vasomotor instability with frequent but transient morbilliform rash when eating or excited

Given the severity of the potential disturbances associated with an effectively disconnected autonomic system, it would seem unreal that something as simple as food, or more specifically, the nutrients in foods, could modify, perhaps even override the consequences of familial dysautonomia, but it does. Both the original expression of the mutation and it’s continued influence on health are mediated by food, likely via interactions with the mitochondria. From the book (Chapter 5, pp 205-207):

Most notably for our purposes, the IKAP/ELP nutrition/starvation stressor-sensing capability extends the possibility that, at least evolutionarily, the splicing error was in response to dietary constraints; one that may yet be modified by overriding those conditions. Indeed, some research suggests this is the case. Specifically, the soy isoflavones genistein and daidzein (phytoestrogens), in addition to tocotrienol (vitamin E), the flavinoid epigallocatechin gallate (EGCG; an antioxidant found in green tea), and the plant cytokinin kinetin (a component of coconut milk), all favorably modulate IKBKAP splicing in familial dysautonomia-derived cells. That is, these compounds, alone or together, increase the proportional number of wild-type to mutated proteins. The combination of EGCG plus genistein restored the ratio of wild-type to mutated proteins equivalent to those in normal cells.

While not directly related to thiamine, the notion that compounds found in consumed foods regulate the transcriptional activity of proteins involved in nutrient sensing with direct and indirect ties to mitochondrial function suggests the inherent modifiability of processes that we heretofore considered hardwired. It is not such a big jump to think that there may be other nutrient compounds capable of supporting healthy development and/or functionally overriding genetic errors.”

Wow. Both the original splicing error and it’s continued persistence may be due to dietary constraints, via cell-based environmental sensors. The implications of this research are staggering. If this proves to be true, it means that some, maybe many or all genes have stressor-sensing capabilities. That is an enormously important discovery, one that shifts the entire paradigm of genetics. Even more interesting, the possibility that genetic errors may be overridden with nutrients. The therapeutic possibilities are endless.

The flip side, of course, is that the lack of nutrients in the typical western diet and the regular exposure to environmental toxicants may have genetic ramifications well beyond our lifetimes. Our behaviors now will affect the health of our grandchildren and their grandchildren. The medications we take, the foods we eat, the chemical exposures are all subtly and not so subtly changing our DNA; changes that may not manifest in any significant way for us, but will become obvious in subsequent generations. That is an awesome responsibility. One that none of us seems too keen to admit. Perhaps that is why the immutability of genetics continues to hold sway.

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Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.